Vps35 in cooperation with LRRK2 regulates synaptic vesicle endocytosis through the endosomal pathway in Drosophila

被引：89

作者：

Inoshita, Tsuyoshi ^{[1
]}

Arano, Taku ^{[2
]}

Hosaka, Yuka ^{[3
]}

Meng, Hongrui ^{[4
]}

Umezaki, Yujiro ^{[4
]}

Kosugi, Sakiko ^{[5
]}

Morimoto, Takako ^{[5
]}

Koike, Masato ^{[6
]}

Chang, Hui-Yun ^{[7
,8
]}

Imai, Yuzuru ^{[1
,3
]}

Hattori, Nobutaka ^{[1
,3
]}

机构：

[1] Juntendo Univ, Grad Sch Med, Dept Res Parkinsons Dis, Tokyo 1138421, Japan

[2] Juntendo Univ, Grad Sch Med, Ctr Genom & Regenerat Med, Tokyo 1138421, Japan

[3] Juntendo Univ, Grad Sch Med, Dept Neurol, Tokyo 1138421, Japan

[4] Juntendo Univ, Grad Sch Med, Res Inst Dis Old Age, Tokyo 1138421, Japan

[5] Tokyo Univ Pharm & Life Sci, Lab Cellular Neurobiol, Hachioji, Tokyo 1920392, Japan

[6] Juntendo Univ, Grad Sch Med, Dept Cell Biol & Neurosci, Tokyo 1138421, Japan

[7] Natl Tsing Hua Univ, Inst Syst Neurosci, Hsinchu 30013, Taiwan

[8] Natl Tsing Hua Univ, Dept Med Sci, Hsinchu 30013, Taiwan

来源：

HUMAN MOLECULAR GENETICS | 2017年 / 26卷 / 15期

关键词：

TO-GOLGI RETRIEVAL; PARKINSONS-DISEASE; RETROMER COMPLEX; WASH COMPLEX; NEUROTRANSMITTER RELEASE; RECEPTOR TRAFFICKING; IN-VIVO; MUTATIONS; DISTINCT; HOMOLOG;

D O I：

10.1093/hmg/ddx179

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Mutations of the retromer component Vps35 and endosomal kinase LRRK2 are linked to autosomal dominant forms of familial Parkinson's disease (PD). However, the physiological and pathological roles of Vps35 and LRRK2 in neuronal functions are poorly understood. Here, we demonstrated that the loss of Drosophila Vps35 (dVps35) affects synaptic vesicle recycling, dopaminergic synaptic release and sleep behavior associated with dopaminergic activity, which is rescued by the expression of wild-type dVps35 but not the PD-associated mutant dVps35 D647N. Drosophila LRRK2 dLRRK together with Rab5 and Rab11 is also implicated in synaptic vesicle recycling, and the manipulation of these activities improves the Vps35 synaptic phenotypes. These findings indicate that defects of synaptic vesicle recycling in which two late-onset PD genes, Vps35 and LRRK2, are involved could be key aspects of PD etiology.

引用

页码：2933 / 2948

页数：16

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